Circulating microRNAs (miRNAs) have been proposed as minimally invasive prognostic markers for various types of cancers, including colorectal cancer (CRC), the third most diagnosed cancer worldwide. We aimed to evaluate the levels of circulating miRNAs that might serve as markers for CRC prognosis and survival. We included plasma samples of 543 CRC patients with stage I-IV disease from a population-based study carried out in Germany. After comprehensive evaluation of current literature, 95 miRNAs were selected and measured with Custom TaqManV R Array MicroRNA Cards. Plasma samples of non-metastatic and metastatic colon cancer patients, each group consisting of ten patients with 'good' and ten patients with 'bad' prognosis were screened. Identified candidate miRNAs were further validated by RT-qPCR in the whole study cohort. The association of the miRNA levels with patients' survival and the prognostic subtypes was analyzed with uni-and multivariate logistic regression and Cox proportional hazards regression models. Increased miR-122 levels were associated with a 'bad' prognostic subtype in metastatic CRC (Odds ratio: 1.563, 95% confidence interval (CI): 1.038-2.347) and a shorter relapse-free survival and overall survival for non-metastatic (Hazard ratio (HR): 1.370, 95% CI: 1.028-1.825; HR: 1.353, 95% CI: 1.002-1.828) and metastatic (HR: 1.264, 95% CI: 1.050-1.520; HR: 1.292, 95% CI: 1.078-1.548) CRC patients. Additionally, several members of the miR-200 family showed associations with patients' prognosis and correlations to clinicopathological characteristics. The here identified miRNA markers, miR-122 and the miR-200 family members, could be of use in the development of a multi-marker blood test for CRC prognosis.Colorectal cancer (CRC) is the third most common cancer worldwide with 1.36 million new cases annually. 1 The worldwide incidence varies up to 10-fold, with almost 55% of the cases occurring in more developed regions. Every year 694,000 CRC patients die from metastasis as the major cause of death. Approximately 20% of diagnoses are made in the metastatic stage with a median survival time of less than 2 years. 2 The lack of effective treatment options for the late CRC stages necessitates to better understand the processes of distant metastasis formation and to identify efficient markers for the patients' prognosis.Several steps during metastasis formation are associated with changes in microRNA (miRNA) expression levels. 3 Altered miRNA abundances have been reported not only in tissues but also for circulating miRNAs, representing the miRNA population in the cell-free component of body fluids such as plasma and serum. In the past years, circulating miRNAs have been investigated as potential candidates for biomarkers for various cancers. [4][5][6][7] Besides the proven role of miRNAs in cancer development and progression, 8 their high stability, easy access through minimally invasive techniques and the potential of repeated sampling makes them almost ideal biomarker candidates. 9,10 Recently, we identi...

Background We examined the associations between germline variants and breast cancer mortality using a large meta-analysis of women of European ancestry. Methods Meta-analyses included summary estimates based on Cox models of twelve datasets using ~10.4 million variants for 96,661 women with breast cancer and 7697 events (breast cancer-specific deaths). Oestrogen receptor (ER)-specific analyses were based on 64,171 ER-positive (4116) and 16,172 ER-negative (2125) patients. We evaluated the probability of a signal to be a true positive using the Bayesian false discovery probability (BFDP). Results We did not find any variant associated with breast cancer-specific mortality at P < 5 × 10 −8 . For ER-positive disease, the most significantly associated variant was chr7:rs4717568 (BFDP = 7%, P = 1.28 × 10 −7 , hazard ratio [HR] = 0.88, 95% confidence interval [CI] = 0.84–0.92); the closest gene is AUTS2 . For ER-negative disease, the most significant variant was chr7:rs67918676 (BFDP = 11%, P = 1.38 × 10 −7 , HR = 1.27, 95% CI = 1.16–1.39); located within a long intergenic non-coding RNA gene (AC004009.3), close to the HOXA gene cluster. Conclusions We uncovered germline variants on chromosome 7 at BFDP < 15% close to genes for which there is biological evidence related to breast cancer outcome. However, the paucity of variants associated with mortality at genome-wide significance underpins the challenge in providing genetic-based individualised prognostic information for breast cancer patients.

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